Study of ethanol induced toxicity in liver explants using microfluidic devices

Current in vitro methodologies for the culture and analysis of liver specific responses lack the sophistication of in vivo dynamics. In this work, a microfluidic based experimental methodology has been utilized to reproduce a biomimetic microenvironment in which pseudo in vivo liver tissue studies can be carried out under in vitro conditions. This innovative technique, which exploits the inherent advantages of microfluidic technology, has been utilised to study the viability and functionality of explant liver tissue over four days in the presence of varying concentrations of ethanol. Concentrations of ethanol as low as 20 mM have produced a decrease in WST-1 metabolism, a marker of mitochondrial activity, and an increase lactose dehydrogenase release, reflecting cell death, in the explant samples; these effects increase with higher ethanol concentrations. A concomitant decrease in albumin and urea synthesis was also observed. We believe the proposed methodology is widely applicable and is clearly of relevance to biological and clinical research including drug development and toxicity, as well as enabling better fundamental understanding of tissue/cell processes.